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A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors

dc.creatorCamacho F.
dc.creatorMoreno E.
dc.creatorGarcia-Alles L.F.
dc.creatorChinea Santiago G.
dc.creatorGilleron M.
dc.creatorVasquez A.
dc.creatorChoong Y.S.
dc.creatorReyes F.
dc.creatorNorazmi M.N.
dc.creatorSarmiento M.E.
dc.creatorAcosta A.
dc.date2020
dc.date.accessioned2021-02-05T14:57:45Z
dc.date.available2021-02-05T14:57:45Z
dc.identifier.issn16643224
dc.identifier.urihttp://hdl.handle.net/11407/5906
dc.descriptionLipids, glycolipids and lipopeptides derived from Mycobacterium tuberculosis (Mtb) are presented to T cells by monomorphic molecules known as CD1. This is the case of the Mtb-specific sulfoglycolipid Ac2SGL, which is presented by CD1b molecules and is recognized by T cells found in tuberculosis (TB) patients and in individuals with latent infections. Our group, using filamentous phage display technology, obtained two specific ligands against the CD1b-Ac2SGL complex: (i) a single chain T cell receptor (scTCR) from a human T cell clone recognizing the CD1b-AcSGL complex; and (ii) a light chain domain antibody (dAbκ11). Both ligands showed lower reactivity to a synthetic analog of Ac2SGL (SGL12), having a shorter acyl chain as compared to the natural antigen. Here we put forward the hypothesis that the CD1b endogenous spacer lipid (EnSpacer) plays an important role in the recognition of the CD1b-Ac2SGL complex by specific T cells. To support this hypothesis we combined: (a) molecular binding assays for both the scTCR and the dAbκ11 antibody domain against a small panel of synthetic Ac2SGL analogs having different acyl chains, (b) molecular modeling of the CD1b-Ac2SGL/EnSpacer complex, and (c) modeling of the interactions of this complex with the scTCR. Our results contribute to understand the mechanisms of lipid presentation by CD1b molecules and their interactions with T-cell receptors and other specific ligands, which may help to develop specific tools targeting Mtb infected cells for therapeutic and diagnostic applications. © Copyright © 2020 Camacho, Moreno, Garcia-Alles, Chinea Santiago, Gilleron, Vasquez, Choong, Reyes, Norazmi, Sarmiento and Acosta.
dc.language.isoeng
dc.publisherFrontiers Media S.A.
dc.relation.isversionofhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85094679922&doi=10.3389%2ffimmu.2020.566710&partnerID=40&md5=4cbb6ca3c226a0faf9e350ff254de0de
dc.sourceFrontiers in Immunology
dc.subjectAc2SGLspa
dc.subjectCD1bspa
dc.subjectendogenous spacerspa
dc.subjectMycobacterium tuberculosisspa
dc.subjectscTCRspa
dc.subjectsulfoglycolipidsspa
dc.titleA Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors
dc.typeArticleeng
dc.rights.accessrightsinfo:eu-repo/semantics/restrictedAccess
dc.identifier.doi10.3389/fimmu.2020.566710
dc.subject.keywordamino acideng
dc.subject.keywordCD1b antigeneng
dc.subject.keywordglucoseeng
dc.subject.keywordglucose monomycolateeng
dc.subject.keywordMycobacterium antigeneng
dc.subject.keywordsulfuric acideng
dc.subject.keywordT lymphocyte receptoreng
dc.subject.keywordunclassified drugeng
dc.subject.keywordArticleeng
dc.subject.keywordcrystal structureeng
dc.subject.keywordenzyme linked immunosorbent assayeng
dc.subject.keywordhumaneng
dc.subject.keywordhypothesiseng
dc.subject.keywordlight chaineng
dc.subject.keywordmolecular dockingeng
dc.subject.keywordMycobacterium tuberculosiseng
dc.subject.keywordprotein lipid interactioneng
dc.subject.keywordprotein structureeng
dc.subject.keywordT lymphocyteeng
dc.subject.keywordtuberculosiseng
dc.relation.citationvolume11
dc.publisher.facultyFacultad de Ciencias Básicasspa
dc.affiliationCamacho, F., Biologicals Sciences School, University of Concepcion, Concepcion, Chile
dc.affiliationMoreno, E., Faculty of Basic Sciences, University of Medellin, Medellin, Colombia
dc.affiliationGarcia-Alles, L.F., TBI, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France
dc.affiliationChinea Santiago, G., Center for Genetic Engineering and Biotechnology, Havana, Cuba
dc.affiliationGilleron, M., Institut de Pharmacologie et Biologie Structurale, Université de Toulouse, Toulouse, France
dc.affiliationVasquez, A., Biologicals Sciences School, University of Concepcion, Concepcion, Chile
dc.affiliationChoong, Y.S., Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Minden, Malaysia
dc.affiliationReyes, F., Biologicals Sciences School, University of Concepcion, Concepcion, Chile
dc.affiliationNorazmi, M.N., School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
dc.affiliationSarmiento, M.E., School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
dc.affiliationAcosta, A., School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
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dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.type.driverinfo:eu-repo/semantics/article


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